Background: Recent transcriptome analyses have shown that long non-coding RNAs (ncRNAs) play extensive roles in transcriptional regulation. In particular, we have reported that promoter-associated ncRNAs (pancRNAs) activate the partner gene expression via local epigenetic changes.

Results: Here, we identify thousands of genes under pancRNA-mediated transcriptional activation in five mammalian species in common. In the mouse, 1) pancRNA-partnered genes confined their expression pattern to certain tissues compared to pancRNA-lacking genes, 2) expression of pancRNAs was significantly correlated with the enrichment of active chromatin marks, H3K4 trimethylation and H3K27 acetylation, at the promoter regions of the partner genes, 3) H3K4me1 marked the pancRNA-partnered genes regardless of their expression level, and 4) C- or G-skewed motifs were exclusively overrepresented between&minus;200 and&minus;1&nbsp;bp relative to the transcription start sites of the pancRNA-partnered genes. More importantly, the comparative transcriptome analysis among five different mammalian species using a total of 25 counterpart tissues showed that the overall pancRNA expression profile exhibited extremely high species-specificity compared to that of total mRNA, suggesting that interspecies difference in pancRNA repertoires might lead to the diversification of mRNA expression profiles.

Conclusions: The present study raises the interesting possibility that the gain and/or loss of gene-activation-associated pancRNA repertoires, caused by formation or disruption of the genomic GC-skewed structure in the course of evolution, finely shape the tissue-specific pattern of gene expression according to a given species.

Electronic supplementary material: The online version of this article (doi:10.1186/s12864-017-3662-1) contains supplementary material, which is available to authorized users.

Fig2: Histone modifications across the regions around TSSs of cerebral cortex-specific genes. RPM (Read count per million mapped reads) derived from ChIP-seq data (H3K4me1, H3K4me3, and H3K27ac) of mouse cerebral cortex (Cortex), cerebellum (Cbellum), heart, kidney, and liver across the regions around TSSs (−2,000 bp to +2,000 bp relative to TSS). In this analysis, cerebral cortex-specific genes, pancRNA-partnered cerebral cortex-specific genes, and pancRNA-lacking cerebral cortex-specific genes were utilized (TSI > 0.9). The standard error of the mean across the regions is shown as semi-transparent shading around the mean curve

Mentions:
We next investigated whether the expression of pancRNAs was associated with the establishment of the histone modification pattern. Using ChIP-seq data in the mouse ENCODE database (Additional file 2: Table S2) [44], we examined the enrichment of the histone modifications at the regions around TSSs of protein-coding genes, pancRNA-partnered genes and pancRNA-lacking genes that represent the tissue-specific expression pattern (TSI > 0.9). Because pancRNAs have been shown to be involved in the active chromatin modification, we focused on mono-methylated H3K4 (H3K4me1), tri-methylated H3K4 (H3K4me3) and acetylated lysine 27 of histone H3 (H3K27ac). At the regions around TSSs of the protein-coding genes, both H3K4me3 and H3K27ac were frequently observed in the tissue where the genes show the maximum expression level in comparison to the other four tissues (Fig. 2, Additional file 5: Figure S3). Intriguingly, in the tissue where the genes show the maximum expression level, H3K4me3 and H3K27ac were more frequently observed at the regions around TSSs of the pancRNA-partnered genes than at those of protein-coding genes and pancRNA-lacking genes (Fig. 2, Additional file 5: Figure S3). These results indicate that the expression of pancRNA is strongly associated with the enrichment of the active chromatin modification, and suggest that the establishment of H3K4me3 and H3K27ac marks might play a key role in triggering expression of pancRNA-partnered genes in a tissue-specific manner. However, considering the expression levels of pancRNA-partnered tissue-specific genes, we cannot completely exclude the possibility that the enrichment of active chromatin marks at these promoters might simply be a sign that pancRNA-partnered genes are more highly expressed than other protein-coding genes (Additional file 6: Figure S4). At the regions around TSSs of pancRNA-partnered genes, H3K4me1 was more frequently observed regardless of the tissue than at the TSSs of protein-coding genes and pancRNA-lacking genes (Fig. 2, Additional file 5: Figure S3). This tendency of H3K4me1 enrichment in the promoter regions of pancRNA-partnered genes raised the possibility that the promoter regions of pancRNA-partnered genes were epigenetically marked as a result of particular sequence features that had enabled them to acquire pancRNA-coding regions in the genomic DNA.Fig. 2

Fig2: Histone modifications across the regions around TSSs of cerebral cortex-specific genes. RPM (Read count per million mapped reads) derived from ChIP-seq data (H3K4me1, H3K4me3, and H3K27ac) of mouse cerebral cortex (Cortex), cerebellum (Cbellum), heart, kidney, and liver across the regions around TSSs (−2,000 bp to +2,000 bp relative to TSS). In this analysis, cerebral cortex-specific genes, pancRNA-partnered cerebral cortex-specific genes, and pancRNA-lacking cerebral cortex-specific genes were utilized (TSI > 0.9). The standard error of the mean across the regions is shown as semi-transparent shading around the mean curve

Mentions:
We next investigated whether the expression of pancRNAs was associated with the establishment of the histone modification pattern. Using ChIP-seq data in the mouse ENCODE database (Additional file 2: Table S2) [44], we examined the enrichment of the histone modifications at the regions around TSSs of protein-coding genes, pancRNA-partnered genes and pancRNA-lacking genes that represent the tissue-specific expression pattern (TSI > 0.9). Because pancRNAs have been shown to be involved in the active chromatin modification, we focused on mono-methylated H3K4 (H3K4me1), tri-methylated H3K4 (H3K4me3) and acetylated lysine 27 of histone H3 (H3K27ac). At the regions around TSSs of the protein-coding genes, both H3K4me3 and H3K27ac were frequently observed in the tissue where the genes show the maximum expression level in comparison to the other four tissues (Fig. 2, Additional file 5: Figure S3). Intriguingly, in the tissue where the genes show the maximum expression level, H3K4me3 and H3K27ac were more frequently observed at the regions around TSSs of the pancRNA-partnered genes than at those of protein-coding genes and pancRNA-lacking genes (Fig. 2, Additional file 5: Figure S3). These results indicate that the expression of pancRNA is strongly associated with the enrichment of the active chromatin modification, and suggest that the establishment of H3K4me3 and H3K27ac marks might play a key role in triggering expression of pancRNA-partnered genes in a tissue-specific manner. However, considering the expression levels of pancRNA-partnered tissue-specific genes, we cannot completely exclude the possibility that the enrichment of active chromatin marks at these promoters might simply be a sign that pancRNA-partnered genes are more highly expressed than other protein-coding genes (Additional file 6: Figure S4). At the regions around TSSs of pancRNA-partnered genes, H3K4me1 was more frequently observed regardless of the tissue than at the TSSs of protein-coding genes and pancRNA-lacking genes (Fig. 2, Additional file 5: Figure S3). This tendency of H3K4me1 enrichment in the promoter regions of pancRNA-partnered genes raised the possibility that the promoter regions of pancRNA-partnered genes were epigenetically marked as a result of particular sequence features that had enabled them to acquire pancRNA-coding regions in the genomic DNA.Fig. 2

Background: Recent transcriptome analyses have shown that long non-coding RNAs (ncRNAs) play extensive roles in transcriptional regulation. In particular, we have reported that promoter-associated ncRNAs (pancRNAs) activate the partner gene expression via local epigenetic changes.

Results: Here, we identify thousands of genes under pancRNA-mediated transcriptional activation in five mammalian species in common. In the mouse, 1) pancRNA-partnered genes confined their expression pattern to certain tissues compared to pancRNA-lacking genes, 2) expression of pancRNAs was significantly correlated with the enrichment of active chromatin marks, H3K4 trimethylation and H3K27 acetylation, at the promoter regions of the partner genes, 3) H3K4me1 marked the pancRNA-partnered genes regardless of their expression level, and 4) C- or G-skewed motifs were exclusively overrepresented between&minus;200 and&minus;1&nbsp;bp relative to the transcription start sites of the pancRNA-partnered genes. More importantly, the comparative transcriptome analysis among five different mammalian species using a total of 25 counterpart tissues showed that the overall pancRNA expression profile exhibited extremely high species-specificity compared to that of total mRNA, suggesting that interspecies difference in pancRNA repertoires might lead to the diversification of mRNA expression profiles.

Conclusions: The present study raises the interesting possibility that the gain and/or loss of gene-activation-associated pancRNA repertoires, caused by formation or disruption of the genomic GC-skewed structure in the course of evolution, finely shape the tissue-specific pattern of gene expression according to a given species.

Electronic supplementary material: The online version of this article (doi:10.1186/s12864-017-3662-1) contains supplementary material, which is available to authorized users.